RESPONSE OF LEPTIN TO SHORT-TERM AND PROLONGED OVERFEEDING IN HUMANS

As one of the postulated roles of the ob gene product, leptin, is regu lation of energy balance and preservation of normal body composition, we investigated the effect of acute and chronic calorie excess (weight gain) on serum leptin in humans. Two protocols were employed: 1) acut e (12-h) massive (120 Cal/kg) voluntary overfeeding of eight healthy i ndividuals; and 2) chronic overfeeding to attain 10% weight gain, with its subsequent maintenance for additional 2 weeks, involving six norm al males. In the acute experiments (protocol 1), circulating leptin ro se by 40% over baseline (P < 0.01) during the final hours of overfeedi ng; this increase persisted until the next morning. At the point of ac hievement and the 2-week maintenance of 10% weight gain (protocol 2), a more than 3-fold rise in the basal leptin concentration was observed (P < 0.01). A direct linear relationship was found between the magnit ude of the leptin response to weight gain and the percent gain of body fat (r = 0.88; P < 0.01). In summary, 1) in contrast to normal food i ntake (8), short term massive overfeeding is associated with a moderat e elevation of circulating leptin levels that persists until next feed ing cycle is initiated; and 2) a 10% weight gain causes different chan ges in the body composition, and the resulting rise in circulating lep tin parallels the increase in the percentage of body fat. In conclusio n, these studies document acute elevation of leptin in response to pos itive energy balance and suggest that developing resistance to leptin is associated with bigger fat deposition during weight gain in humans.